This proposal requests support for a Keystone Symposia meeting entitled Dendritic Cells and the Initiation of Adaptive Immunity, organized by Ira Mellman, Michel C. Nussenzweig, Virginia Pascual and Federica Sallusto, which will be held in Santa Fe, New Mexico from February 12 - 17, 2011. Current studies of Dendritic Cells (DCs) have confirmed not only their major role as antigen presenting cells in adaptive immunity but also their important functions in maintaining tolerance and in the initiation of the innate resistance and inflammatory responses. Thus, DCs function as an important bridge between innate resistance and adaptive immunity, either through cellular interactions or secretion of pro-inflammatory and immunoregulatory cytokines. The origin and migration pattern of DCs, their cell biological mechanisms of action, their functional diversity, their specializations and activities in specific tissue contexts, as well as their sharing of hematopoietic lineages, functions, and receptors with other phagocytic cell types such as monocytes and macrophages are subjects of intense investigation. Increasingly, the roles of DCs in disease pathology and as potential therapeutic targets are being explored both in the laboratory and in the clinic. This is particularly true in human cancer, where both active and passive immunotherapies involving DCs are finally being put to the test in a systematic fashion. In this symposium, each of these aspects of DC biology and immunological function will be explored in detail, including taking a number of in-depth looks at functions (such as innate activation mechanisms) that are key to understanding how DCs perform their many remarkable tasks. In addition, the Dendritic Cells symposium will combine and synergize with a second, jointly organized symposium entitled Cancer Control by Tumor Suppressors and Immune Effectors, thereby emphasizing emerging concepts concerning the role of the immune response in cancer and cancer therapy. Thus, opportunities for interdisciplinary interactions will be significantly enhanced by the concurrent meeting, which will share an opening and closing keynote address, two plenary sessions, and a workshop with this meeting. Project Narrative: Dendritic cells lie at the very basis of all antigen-specific immune responses, regulating both protective immunity against invading pathogens and tolerance to beneficial antigens, such as those in food proteins and in the proteins resident in human tissue. Failure of either of these key functions leads to a wide variety of diseases. The Keystone Symposia meeting on Dendritic Cells and the Initiation of Adaptive Immunity will critically examine how dendritic cells contribute to immunity and disease. This meeting will promote a better appreciation for the roles of dendritic cells in health and disease, and to the development of dendritic cells as targets for therapeutic intervention.